SEATTLE & SALT LAKE CITY—Aimed at “bringing 21st-century medicine to the healthcare system,” Dr. Leroy Hood, co-founder of both the Institute for Systems Biology and Integrated Diagnostics, in collaboration with Sera Prognostics, has announced the successful results of a study on the blood-based Xpresys Lung and PreTRM tests. A resulting paper entitled, “The building blocks of successful translation of proteomics to the clinic,” is to be published in the June issue of Current Opinion in Biotechnology.
“This publication validates the use of a systems biology approach as a valuable strategy for successfully developing multiplexed selective reaction monitoring mass spectrometry(SRM-MS) diagnostics by helping to identify and prioritize relevant biomarkers and by informing discovery study design,” states Hood. “This disease-agnostic technique holds value in supporting the development of proteomic tests across disease states and significantly advancing care for patients.”
The Xpresys Lung and PreTRM tests are expected to save billions of dollars in unnecessary procedures for lung disease patients and future health problems for premature births, says Hood, who is also chief science officer of Providence St. Joseph Health in Seattle.
Nevertheless, the appearance of diagnostic tests based on SRM-MS technology in the clinic has lagged, considering the first two multiplexed SRM-MS diagnostic tests used in clinical practice, Xpresys1 Lung and PreTRM, were launched in 2013 and 2015, respectively, states the journal article.
Xpresys Lung is a blood test for assessing the cancer risk of lung nodules discovered by radiology such as CT scans. Lung nodules are small masses of tissue in the lung, often referred to as a “shadow” or “spot” on the lung. While the majority of these nodules are benign, a relatively small percentage can be malignant.
“Each year approximately 1.6 million lung nodules are detected in the U.S., alone, and that is expected to increase strikingly as the national screening program is fully implemented,” the journal article states. “The majority of these nodules are benign, with an estimated 15 to 25 percent being malignant. Lack of precise diagnostics, however, results in a 35 to 42 percent of benign nodules being overtreated with invasive procedures such as biopsies and surgeries.”
Xpresys Lung “measures the relative expression of 11 proteins by SRM-MS, five being diagnostic and six used for normalization of signal, and uses this information to generate a probability estimate that a lung nodule is benign, providing molecular evidence for whether or not invasive procedures can be avoidable,” the paper states. “Interestingly, all five of these proteins are expressed in disease-perturbed networks found in lung cancer.”
The PreTRM test, performed at 19 weeks of pregnancy, determines if it is likely a pregnant woman will have a preterm birth, says Hood. Spontaneous preterm birth (sPTB) is a leading cause of infant mortality and morbidity worldwide, and in the United States, preterm birth is the leading cause of neonatal death and death in children before age five, with the health-economic impact estimated by the National Academy of Medicine in 2005 to be in excess of $26 billion per year.
Prior to the development of PreTRM, intense research into the development of predictive algorithms based on clinical and demographic factors, or using measured serum or vaginal biomarkers, did not result in clinically useful tests, the journal authors state.
PreTRM, on the other hand, measures the relative level of two proteins by SRM-MS. These measurements are combined into a risk estimate that a pregnancy will end in sPTB, the journal article states. High-risk pregnancies can then be treated with interventions such as progesterone and/or high-intensity case management.
Paul Kearney, president, chief science officer and co-founder of Integrated Diagnostics, states, “The importance of highly multiplexed proteomics for understanding complex diseases and conditions, such as cancer and pregnancy, cannot be overstated.”
The general process “described in this paper provides the blueprint for the successful development of proteomic solutions for a diverse range of clinically unmet challenges,” Kearney adds.
Gregory C. Critchfield, chairman and CEO of Sera Prognostics, states, “Together with Integrated Diagnostics and the Institute of Systems Biology, we are proud to have pioneered novel mass spectrometry proteomic diagnostic tests using rigorous systems-biology approaches. SRM-MS is scalable and cost-effective, moving from a research tool into clinical production settings.”
“This work offers a roadmap for developing future tests, enabling better diagnosis and stratification of patients according to disease sub-types, responses to therapy and potential outcomes,” Critchfield adds. “The technology holds great promise for meaningful advances in precision and personalized medicine in patients with conditions that have been traditionally very difficult to diagnose.”
Hood is also developing a proteomic path to diagnosing post-traumatic stress disorder, brain cancer and a series of blood tests for liver diseases.